Is GRM6 p.Asp377= (c.1131C>T) pathogenic?

GRM6 p.Asp377= (c.1131C>T) is classified Benign in GRM6 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 75.9%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with congenital stationary night blindness 1B.

What condition is associated with GRM6 p.Asp377= (c.1131C>T)?

GRM6 p.Asp377= (c.1131C>T) is associated with congenital stationary night blindness 1B (ClinVar).

GRM6 p.Asp377=

Q: How common is GRM6 p.Asp377= (c.1131C>T) in the general population?

GRM6 p.Asp377= (c.1131C>T) is common (popmax 75.9%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1131C>T · rs2071246 · VCV99625

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 75.9%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

congenital stationary night blindness 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.8	GERP -3.6
Overall
CADD	0.349	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 75.9% European (non-Finnish) · 894,741/1,179,002 alleles

Filtering AF 75.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 75.7%

Overall 74.5% 1,200,299/1,610,862 alleles · common exomes 1,089,419/1,461,070 · genomes 110,880/149,792 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	79.4%	1
European (non-Finnish)grpmax	75.9%	1
African / African-American	75.3%	1
Remaining individualsnot grpmax-eligible	74%	1
Admixed American	67.4%	1
East Asian	66.8%	1
Middle Eastern	66.5%	2
South Asian	65.5%	2
Ashkenazi Jewishnot grpmax-eligible	64.4%	2
Amishnot grpmax-eligible	43.5%	2

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GRM6
Protein: p.Asp377=
Coding: c.1131C>T
MANE Select: NM_000843
dbSNP: rs2071246
Type: single nucleotide variant
Location: chr5:178989287 (GRCh38)
Gene constraint: LOEUF 1.229 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 5 PDB

Full GRM6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital stationary night blindness 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRM6 p.Arg446Ter Pathogenic ★★ same condition
GRM6 p.Arg621Ter Pathogenic ★★ same condition
GRM6 p.Gln708Ter Pathogenic ★★ same condition
GRM6 p.Pro46Leu Likely pathogenic ★★ same condition
GRM6 p.Ala175Gly Uncertain significance ★★ same condition
GRM6 p.Arg677His Uncertain significance ★★ ⚠ same condition
GRM6 p.Cys522Tyr Uncertain significance ★★ ⚠ same condition
GRM6 p.Glu781Lys Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/grm6-p-asp377 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown